This proposal is to use the heterotopic (abdominal aorta) rat heart transplant model to study methods of organ preservation for transplantation and measures which may increase organ transplant survival as they relate to mediators of inflammation and to receptors for these mediators on lymphocytes. Organ preservation studies will involve investigation of the effects of duration of pre-transplant warm and cold ischemia, of wash-out solutions (intra-and extra-cellular electrolytes) and of machine preservation on organ survival and vasoactive substances metabolism. Allograft, isograft, host lymphoid tissue and blood levels and metabolism of mediators of inflammation (histamine, bradykinin, PGEl and serotonin) as well as related alterations in cyclic AMP metabolism will be studied. Lymphocyte receptors for histamine will be studied by various extraction, separation and assay techniques to determine their sites of concentration (allograft, spleen, thymus, lymph nodes, blood, etc.), their numbers, their homing characteristics on transfer to isogenic animal which have received heart allografts or have received subcutaneous injections of vasoactive substances (alone or in combination) and their cytolytic activity alone and in combination in vitro with added histamine, bradykinin, PGEl and serotonin (separately and in combination). These studies and those relating to vasoactive substances metabolism will be done on a daily basis for the initial 12 days post grafting in non-immunosuppressed animals. Anti-histamines (H1 and and H2 receptor blockers) and anti-serotonin,-PGE and-kinin drugs will be used alone and in combination to study their effects on allograft survival and on the above levels of vasoactive substances metabolism and lymphocyte receptors for histamine.